Gut Immune Cells Keep Beneficial Microbes in Their Place

Things are more complicated than they look. This study, at least in parts, answered a question I had for a long time. Does it matter where bacteria locate in our intestine? The answer is yes but not only this, if "good" bacteria move to the wrong place, they can cause chronic inflammation. So good bacteria become bad.

Therefore I highly doubt that it's enough for all of us to just ingest some probiotics and believe that they heal us. There are 500 to 1000 different species of bacteria in our intestine while you can buy a maximum of 10-20 species in form of probiotics. How do you make sure that these bacteria settle at the right place in your intestine? You can't. You can only hope that they reach the right spot and don't cause any problems.

Lymphoid cells seem to be at the forefront of our intestine. They make sure, that bacteria stay at their right place. Unfortunately the researchers say, that chronic human diseases can deplete or interfere with these lymphoid cells and can lead to chronic inflammation by translocation of bacteria to systemic tissues. This will provoke a Alcaligenes-specific immune response, which is highly inflammatory.

If we take a look at all the latest findings for inflammatory bowel diseases, we find a few things, that nearly all these studies have in common.

1) Translocation of bacteria into the blood stream or systemic tissues is highly detrimental for human health but seems to be a key issue for IBS, IBD, Crohn'S, allergies, cancer etc.. Therefore it would be highly recommended to find a medication that improves gut integrity to a high degree and reduces intestinal permeability.

2) The presence of certain bacteria, their numbers and their location in the intestine are highly important for human health. SIBO seems to be much more prevalent and causative in certain diseases like IBS, than we previously thought.

As a consequence of the little progress we made in the treatment field of gut specific diseases, it is my personal opinion, that reducing bacterial load, especially in the small intestine, as well as improving gut integrity through new medication like Linaclotide (December 2012) is the first important step to make, in order to reduce inflammation. Moreover I believe, that antibiotics like Rifaximin are far superior, compared to other ABs, especially when treating SIBO. In the end, a multiaimed approach needs to be implemented.

Reduce numbers of bad bacteria (ABs), improve location (concentrate on lymphoid cells) and strengthen gut integrity (Linaclotide).

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http://www.sciencedaily.com/releases/2012/06/120606142658.htm

ScienceDaily (June 6, 2012) — The healthy human intestine is colonized with over 100 trillion beneficial, or commensal, bacteria of many different species. In healthy people, these bacteria are limited to the intestinal tissues and have a number of helpful properties, including aiding in the digestion of food and promoting a healthy immune system.

However, when it comes to commensal bacteria, location is key. While commensal bacteria in the intestine provide positive effects, several chronic human diseases, including HIV/AIDS, inflammatory bowel disease, viral hepatitis, and obesity are associated with the spread of these intestinal commensal bacteria to the blood stream and other peripheral tissues, which can cause chronic inflammation. 'Good bugs' that promote normal health can 'turn bad' if found in the wrong location.
In earlier work, researchers from the Perelman School of Medicine at the University of Pennsylvania found that barrier surfaces -- the skin, gut, and lung -- are guarded by immune cells and limit the inner body's exposure to viruses, bacteria, and parasites, as well as allergens and pollutants. But, how immune cells play a role in limiting the location of commensal bacteria to intestinal and other barrier sites remains unclear.
Now, David Artis, PhD, associate professor of Microbiology, and Gregory F. Sonnenberg, PhD, a postdoctoral researcher in the Artis lab, have identified that immune cells, called innate lymphoid cells, are resident in the intestinal tissues of healthy humans, mice, and non-human primates, and are critical in limiting the location of commensal bacteria. If the innate lymphoid cells are depleted in mice, commensal bacteria move to peripheral tissues and promote inflammation. The research appears this week in Science.
Remarkably, the commensal bacteria that were found in peripheral tissues were all members of a group called Alcaligenes, indicating that the immune system may have developed highly selective pathways to regulate containment of different groups of commensal bacteria.
"A fundamental question that has puzzled researchers for many years is how did the human body evolve to accommodate all these commensal bacteria and keep them in their correct locations?," asks Artis. "The indication from these studies is that the body may have many different pathways to limit the spread of commensal bacteria and these pathways may be tailored to specific types of bacteria."
Supporting experiments in animal models, Alcaligenes-specific immune responses were associated with patients with Crohn's disease or progressive hepatitis C virus infection, two debilitating human diseases linked to the spread of commensal bacteria to systemic tissues.
"The identification of systemic Alcaligenes-specific immune responses in these patient populations suggests that, coupled with other groups of bacteria, the spread of Alcaligenes to tissues outside the intestine may be contributing to chronic inflammation and disease progression," suggests Sonnenberg.
Innate immune cells may become impaired in chronic human diseases, resulting in the spread of Alcaligenes bacteria and pathologic inflammation, which may represent a novel pathway to target in human disease, say the investigators.
"Although it's still early days for this line of research, these findings suggest that targeting innate lymphoid cell responses or directly targeting specific groups of commensal bacteria may be useful in the treatment of some chronic inflammatory diseases," adds Artis.
The research was funded by the National Institute of Allergy and Infectious Disease (AI061570, AI087990, AI074878, AI083480, AI095466, AI095608, T32-AI007532, T32-RR007063, K08-DK093784, AI47619); the NIH-funded Penn Center for AIDS Research (P30 AI 045008); the Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award; the Philadelphia VA Medical Research and Merit Review; and the American Gastroenterological Association.

This is very interesting and possibly very relevant here, thanks for posting!

(and I can't wait for Linaclotide )

Very interesting thanks for posting Waverunner. (A bit of serendipity - Amoxicillin following infected teeth - root removals with masses of Probiotics afterwards did improve my GI problems).

There are two question we have to ask ourselves in order to get an efficient treatment strategy.

1) What causes these gut problems?
2) How do we treat them?

The perfect approach, without any doubt, would be to remove the underlying cause. The problem however is, that we don't know what the underlying cause is. Unless some groundbreaking studies come out, it is pure speculation. Sure, infections could be the cause but we still don't know enough and efficient treatment for viral infections are still lacking.

What do we know for sure? We know for sure that SIBO, IBS, increased intestinal permeability etc. are not good for us.

By taking Rifaximin we target a specific problem. This problem is not very far upstream but it's a problem that can be defined. Too much bacteria at the wrong place.

Why are there too much bacteria at the wrong place? This question is a good one. What comes to my mind is reduced motility and malfunctioning of lymphoid cells. To my knowledge there are currently no treatments that target lymphoid cells but there are treatments which target motility. Women have a possibility for treating motility problems by takingTegaserod (targets serotonin signalling but is not available for men). The other treatment options for motility problems are very flawed in my eyes but could work for some.

In the end however we only have one working treatment option right now. ABs, especially Rifaximin. The SIBO problem will vanish for a certain amount of time.

Questions that remain:

- How do we treat increased intestinal permeability?
- How do we improve the functions of goblet cells and lymphoid cells to prevent allergies and translocation of bacteria?
- How do we treat motility problems?
- What is the underlying cause of these issues?

Nanonug posted a very interesting video interview with Dr. Pimentel on the other thread.

!

This is very interesting. But it only talks about the probiotic bacteria causing inflammation when they leak out of the gut and into the blood stream and other tissues. What about the harmful bacteria in the gut? Surely they are all leaking out too? Aren't they worse when they escape into the blood stream?

Great info. Thanks. Wouldn't the bacteria that should be residing in the proper area keep
the other bad guys out ? Also, bacteria need certain environments to live. I only know this
because h pylori loves the stomach.

The info on leaky gut provided by DAN should tell us how to treat this. This approach
includes removing food intolerances, treating bad bacteria and candida, lowering oxalates, addressing
nutritional deficiencies and removing heavy metals.

The only problem I see
with DANs approach is allowing nonfoods, such as grains / sweets into these kids diet.

Still waking up here .. Tc .. X

this is probably relevant
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860105/?tool=pubmed

Great call on Linaclotide. I read about it a few months back and immediately thought of the bacterial translocation in CFS. Ditto for HIV. There are likely bacteria that reside in some of our guts that interfere with this pathway.

When is this going to be available?

Enid, the same exact thing happened with me!!

Drew

Amoxicillin helped me, too. Erythromycin on the other hand didn't.